Fucoidan ameliorates pancreatic beta-cell death and impaired insulin synthesis in streptozotocin-treated beta cells and mice via a Sirt-1-dependent manner

Abstract

Scope: Several beneficial biological functions of fucoidan (FO) isolated from brown algae have been demonstrated. The purpose of this study was to investigate whether FO derived from Sargassum hemiphyllum ameliorates pancreatic beta-cell damage and impaired insulin synthesis under diabetic condition. Methods and results: The effects of FO were studied in streptozotocin (STZ)-treated pancreatic beta-cell line, NIT-1cells, and mice. The cell apoptosis, protein analyses, histological examination, and pancreatic function assays were performed. The increased pancreatic beta-cell apoptosis and decreased insulin secretion observed in STZ-treated NIT-1 cells and mice were greatly attenuated by FO. Moreover, FO has an ability to enhance glucagon-like peptide-1 receptor (GLP-1R) and sirtuin 1 (Sirt-1) activity through activation of AMPK/GAPDH/PDX-1 cascade in STZ-treated beta cells. However, the effects of FO were significantly reversed by EX527, a specific Sirt-1 inhibitor. Similarly, the hyperglycemia, lower expression of Sirt-1, PDX-1, and GLP-1R in the pancreas of diabetic mice were markedly improved after FO administration. Conclusion: We demonstrated that FO exhibits an anti-diabetic effect mainly through attenuation of beta-cell death, thereby elevating insulin synthesis by upregulating PDX-1 and GLP1-R via a Sirt-1-dependent manner. Therefore, FO-containing food or supplements may have a therapeutic effect for diabetes by preventing beta-cell damage and dysfunction.